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A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression

Abstract : A novel 2,3-benzodiazepine-4 derivative, named 1g, has recently been shown to function as an anti-proliferative compound. We now show that it perturbs the formation of a functional mitotic spindle, inducing a spindle assembly checkpoint (SAC)-dependent arrest in human cells. Live analysis of individual microtubules indicates that 1g promotes a rapid and reversible reduction in microtubule growth. Unlike most anti-mitotic compounds, we found that 1g does not interfere directly with tubulin or perturb microtubule assembly in vitro The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests that it targets a conserved microtubule regulation module in humans and flies. Altogether, our results indicate that 1g is a novel promising anti-mitotic drug with the unique properties of altering microtubule growth and mitotic spindle organization.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-02543756
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Submitted on : Friday, April 17, 2020 - 10:13:00 AM
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Vittoria Pirani, Mathieu Métivier, Emmanuel Gallaud, Alexandre Thomas, Siou Ku, et al.. A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression. Journal of Cell Science, Company of Biologists, 2020, 133 (7), pp.jcs239244. ⟨10.1242/jcs.239244⟩. ⟨hal-02543756⟩

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